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Reviewed, UniProtKB/Swiss-Prot P08148 (GP63_LEIMA)

Last modified June 16, 2009. Version 81. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Leishmanolysin
    EC=3.4.24.36
Alternative name(s):
    Cell surface protease
    Major surface glycoprotein
    Protein gp63
    Promastigote surface endopeptidase
    Major surface protease
Gene names
Name: gp63
OrganismLeishmania major
Taxonomic identifier5664 [NCBI]
Taxonomic lineageEukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Leishmania

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Protein attributes

Sequence length602 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Has an integral role during the infection of macrophages in the mammalian host.

Catalytic activity

Preference for hydrophobic residues at P1 and P1' and basic residues at P2' and P3'. A model nonapeptide is cleaved at -Ala-Tyr-|-Leu-Lys-Lys-.

Cofactor

Binds 1 zinc ion per subunit.

Subcellular location

Cell membrane; Lipid-anchor › GPI-anchor. Ref.3

Post-translational modification

The phosphatidylinositol moiety of the GPI-anchor contains a fully saturated, unbranched 1-O-alkyl chain (mainly C24:0) and a mixture of fully saturated unbranched 2-O-acyl chains (C12:0, C14:0, C16:0, and C18:0).

Sequence similarities

Belongs to the peptidase M8 family.

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Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell membrane
Membrane
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
GPI-anchor
Glycoprotein
Lipoprotein
Zymogen
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological processcell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular componentanchored to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionmetalloendopeptidase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from electronic annotation. Source: UniProtKB-KW

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3939 Potential
Propeptide40 – 10061Activation peptide Ref.1
PRO_0000028667
Chain101 – 577477Leishmanolysin
PRO_0000028668
Propeptide578 – 60225Removed in mature form
PRO_0000028669

Sites

Active site2651
Metal binding2641Zinc; catalytic
Metal binding2681Zinc; catalytic
Metal binding3341Zinc; catalytic

Amino acid modifications

Lipidation5771GPI-anchor amidated asparagine
Glycosylation3001N-linked (GlcNAc...) Ref.5 Ref.6
Glycosylation4071N-linked (GlcNAc...) Ref.5 Ref.6
Glycosylation5341N-linked (GlcNAc...) Ref.6
Disulfide bond125 ↔ 142 Ref.6
Disulfide bond191 ↔ 230 Ref.6
Disulfide bond314 ↔ 386 Ref.6
Disulfide bond393 ↔ 455 Ref.6
Disulfide bond406 ↔ 425 Ref.6
Disulfide bond415 ↔ 489 Ref.6
Disulfide bond466 ↔ 510 Ref.6
Disulfide bond515 ↔ 565 Ref.6
Disulfide bond535 ↔ 558 Ref.6

Experimental info

Mutagenesis2541Y → D: No significant effect on protein expression levels or catalytic activity. Ref.4
Mutagenesis2641H → F or Y: No detectable overexpression of mutant protein and hence little catalytic activity. Ref.4
Mutagenesis2651E → D: No significant effect on protein expression levels but almost abolishes catalytic activity. Ref.4
Mutagenesis2681H → N or Y: No detectable overexpression of mutant protein and hence little catalytic activity. Ref.4
Mutagenesis3001N → Q: Increases electrophoretic mobility of the protein. Ref.4
Mutagenesis4071N → Q: Increases electrophoretic mobility of the protein. Ref.4
Mutagenesis5341N → Q: Increases electrophoretic mobility of the protein. Ref.4
Mutagenesis5771N → L: Causes extracellular release of the protein. Ref.4

Secondary structure

1 ...................................................................................................... 602
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P08148-1 [UniParc].

Last modified April 1, 1990. Version 2.
Checksum: 982EF3245D87C43E

FASTA60263,953
        10         20         30         40         50         60 
MSVDSSSTHR RRCVAARLVR LAAAGAAVTV AVGTAAAWAH AGALQHRCVH DAMQARVRQS 

        70         80         90        100        110        120 
VADHHKAPGA VSAVGLPYVT LDAAHTAAAA DPRPGSARSV VRDVNWGALR IAVSTEDLTD 

       130        140        150        160        170        180 
PAYHCARVGQ HVKDHAGAIV TCTAEDILTN EKRDILVKHL IPQAVQLHTE RLKVQQVQGK 

       190        200        210        220        230        240 
WKVTDMVGDI CGDFKVPQAH ITEGFSNTDF VMYVASVPSE EGVLAWATTC QTFSDGHPAV 

       250        260        270        280        290        300 
GVINIPAANI ASRYDQLVTR VVTHEMAHAL GFSGPFFEDA RIVANVPNVR GKNFDVPVIN 

       310        320        330        340        350        360 
SSTAVAKARE QYGCDTLEYL EVEDQGGAGS AGSHIKMRNA QDELMAPAAA AGYYTALTMA 

       370        380        390        400        410        420 
IFQDLGFYQA DFSKAEVMPW GQNAGCAFLT NKCMEQSVTQ WPAMFCNESE DAIRCPTSRL 

       430        440        450        460        470        480 
SLGACGVTRH PGLPPYWQYF TDPSLAGVSA FMDYCPVVVP YSDGSCTQRA SEAHASLLPF 

       490        500        510        520        530        540 
NVFSDAARCI DGAFRPKATD GIVKSYAGLC ANVQCDTATR TYSVQVHGSN DYTNCTPGLR 

       550        560        570        580        590        600 
VELSTVSNAF EGGGYITCPP YVEVCQGNVQ AAKDGGNTAA GRRGPRAAAT ALLVAALLAV 


AL

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References

[1]"Molecular cloning of the major surface antigen of leishmania."
Button L.L., McMaster W.R.
J. Exp. Med. 167:724-729(1988) [PubMed: 3346625] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 101-123.
[2]Button L.L., McMaster W.R.
J. Exp. Med. 171:589-589(1990)
Cited for: SEQUENCE REVISION.
[3]"Structure of the glycosyl-phosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease."
Schneider P., Ferguson M.A.J., McConville M.J., Mehlert A., Homans S.W., Bordier C.
J. Biol. Chem. 265:16955-16964(1990) [PubMed: 2145267] [Abstract]
Cited for: GPI-ANCHOR AT ASN-577.
[4]"Posttranslational regulation of a Leishmania HEXXH metalloprotease (gp63). The effects of site-specific mutagenesis of catalytic, zinc binding, N-glycosylation, and glycosyl phosphatidylinositol addition sites on N-terminal end cleavage, intracellular stability, and extracellular exit."
McGwire B.S., Chang K.-P.
J. Biol. Chem. 271:7903-7909(1996) [PubMed: 8626468] [Abstract]
Cited for: MUTAGENESIS OF TYR-254; HIS-264; GLU-265; HIS-268; ASN-300; ASN-407; ASN-534 AND ASN-577.
[5]"A unique, terminally glucosylated oligosaccharide is a common feature on Leishmania cell surfaces."
Funk V.A., Thomas-Oates J.E., Kielland S.L., Bates P.A., Olafson R.W.
Mol. Biochem. Parasitol. 84:33-48(1997) [PubMed: 9041519] [Abstract]
Cited for: GLYCOSYLATION AT ASN-300 AND ASN-407.
[6]"Crystallization and preliminary X-ray diffraction studies of leishmanolysin, the major surface metalloproteinase from Leishmania major."
Schlagenhauf E., Etges R., Metcalf P.
Proteins 22:58-66(1995) [PubMed: 7675788] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), DISULFIDE BONDS, GLYCOSYLATION AT ASN-300; ASN-407 AND ASN-534.
[7]"The crystal structure of the Leishmania major surface proteinase leishmanolysin."
Schlagenhauf E., Etges R., Metcalf P.
Structure 6:1035-1046(1998) [PubMed: 9739094] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS).

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Cross-references

Sequence databases

Y00647 Genomic DNA. Translation: CAA68673.1.
PIRPL0221.

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1LMLX-ray1.86A100-577[»]
ModBaseSearch...

Protein family/group databases

MEROPSM08.001.

PTM databases

GlycoSuiteDBP08148.

Enzyme and pathway databases

BRENDA3.4.24.36. 19061.

Family and domain databases

InterProIPR006025. Pept_M_Zn_BS.
IPR001577. Peptidase_M8.
[Graphical view]
PANTHERPTHR10942. Peptidase_M8. 1 hit.
PfamPF01457. Peptidase_M8. 1 hit.
[Graphical view]
PRINTSPR00782. LSHMANOLYSIN.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

PMAP-CutDBP08148.

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Entry information

Entry nameGP63_LEIMA
AccessionPrimary (citable) accession number: P08148
Secondary accession number(s): P15906
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: April 1, 1990
Last modified: June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

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Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents